Case report of fatal myocarditis with toripalimab and axitinib combination therapy.

RATIONALE: Cardiac immune-related adverse events (irAEs) are rare but potentially life-threatening complications of immune checkpoint inhibitor (ICI) therapy, with myocarditis associated with particularly high mortality even under aggressive treatment. PATIENT CONCERNS: A 65-year-old male with advanced clear cell renal cell carcinoma and liver metastasis presented with progressive wheezing and fatigue following 4 cycles of combination therapy with toripalimab and axitinib, symptoms that failed to respond to conventional supportive measures. DIAGNOSES: Grade 4 ICI-associated myocarditis was confirmed through a combination of clinical manifestations, characteristic echocardiographic abnormalities, elevated cardiac biomarkers, and the exclusion of infectious causes via comprehensive serological evaluation. INTERVENTIONS: The patient received multimodal immunosuppressive and supportive therapy, including high-dose methylprednisolone, intravenous immunoglobulin (IVIG), venoarterial extracorporeal membrane oxygenation (VA-ECMO), and therapeutic plasma exchange. Concurrently, broad-spectrum antibiotics were administered based on continuous microbial surveillance. OUTCOMES: Although transient hemodynamic stabilization was achieved, the patient subsequently developed severe nosocomial infections and progressive multiorgan failure, leading to death on day 24 of hospitalization. LESSONS: This case underscores the necessity for early recognition and intensive monitoring in managing high-grade ICI-associated myocarditis. It further highlights the critical role of infection prevention strategies, particularly the implementation of microbial surveillance-guided antibiotic prophylaxis, in patients undergoing combination immunotherapy regimens. PLAIN LANGUAGE SUMMARY: We report a 65-year-old male with advanced renal cell carcinoma who developed ICI-associated myocarditis following 4 cycles of combination immunotherapy. The patient presented with progressive dyspnea and fatigue, necessitating hospitalization. Comprehensive diagnostic evaluation confirmed grade 4 myocarditis based on clinical features, elevated cardiac biomarkers, echocardiographic abnormalities, and exclusion of infectious causes. Treatment consisted of multimodal immunosuppressive and life-support therapies, including high-dose methylprednisolone, intravenous IVIG, therapeutic plasma exchange, VA-ECMO, and empiric broad-spectrum antibiotics guided by microbial surveillance. Despite transient hemodynamic stabilization, the patient ultimately progressed to multiorgan failure and died on day 24 of hospitalization. This case underscores the life-threatening nature of ICI-associated myocarditis and highlights the critical need for early recognition, aggressive supportive management, and proactive anti-infective prophylaxis in patients receiving combination immunotherapy.